Transplantation tolerance correlates with high levels of T- and B-lymphocyte activity

Abstract

Mice tolerized (treated to make them tolerant) at birth to transplantation antigens by injection of semiallogeneic cells contain very high numbers of activated T and B lymphocytes in their spleen. Lymphoid hyperactivity correlates with the tolerant state: it is present only in animals accepting skin allografts. Tolerized mice that reject the allogeneic skin graft have approximately the same numbers of total and activated lymphocytes as normal mice. The high level of lymphocyte activation in tolerant mice persists for up to 1 year of age, although it declines with age, and is markedly increased by a secondary allograft. The magnitudes of both primary and secondary tolerant responses are significantly higher than the immunological response of a normal mouse rejecting the same type of allograft. These observations contradict concepts of clonal deletion or anergy as the basis of neonatally induced transplantation tolerance and may contribute additional approaches to experimentation and control of transplantation reactions.